Prostate cancer has become the most common cancer and is the second leading cause of death from cancer in American men [1]. The standard of care is surgery and/or radiation therapy. However, disease recurrence after surgery or radiation still takes place in up to 30% of patients. Although androgen-deprivation therapy is effective, most of these patients eventually develop androgen-refractory prostate cancer. Therefore, more effective and less toxic therapies are urgently needed.
Immunotherapy has been shown to be a promising approach to the treatment of prostate cancer, especially for patients with metastatic castration-resistant prostate cancer [2-4], but until recently it has been met with only sporadic clinical success [4-6]. Recent Food and Drug Administration (FDA) approvals of the immunotherapy-based vaccine/drug sipuleucel-T (Provenge) and ipilimumab (Yervoy) represent milestones in the field of cancer immunotherapy [7,8]. Furthermore, a phase III clinical trial of the gp100 peptide for melanoma also produced highly encouraging clinical results [9]. However, the clinical benefits reported for these agents have fallen far short of complete responses and permanent cures. In the case of sipuleucel-T, the survival benefit for patients was only 4.1 months, without objective tumor regression or substantial changes in prostate specific antigen (PSA) levels. A recent study using animal models further reveals the importance of tumor-specific antigens in eliciting immune responses against a developing tumor [10], spurring more efforts to identify such antigens for cancer immunotherapy. Furthermore, since some major rejection antigens may be lost or altered due to T cell selection and killing [11], the best strategy is to target multiple tumor antigens that are present on individual tumors for immunotherapy.
A number of prostate specific tumor antigens have been well-defined, including PSA [12,13], prostein [14,15], prostate stem cell antigen (PSCA) [16], prostate-specific membrane antigen (PSMA) [17-19], prostatic acid phosphatase (PAP) [20] and transient receptor potential p8 (trp-p8) [21]. Furthermore, HLA-class I-restricted epitopes derived from these tumor antigens have been described [22]. One drawback of single tumor antigen-based immunotherapy is that immune escape may occur. Hence, there is a need to identify additional prostate cancer-specific antigens for development of more effective and antigen-specific vaccines for metastatic prostate cancer.